Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 (preprint)

Although vaccines have reduced COVID-19 disease burden, their efficacy in helminth infection endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal hookworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of SARS-CoV-2. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4+ and CD8+ T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared to animals immunized without Hpb infection. Helminth mediated suppression of spike-specific CD8+ T cell responses occurred independently of STAT6 signaling, whereas blockade of IL-10 rescued vaccine-induced CD8+ T cell responses. In mice, intestinal helminth infection impairs vaccine induced T cell responses via an IL-10 pathway and compromises protection against antigenically shifted SARS-CoV-2 variants.

The indirect impacts of nonpharmacological COVID-19 control measures on other infectious diseases in Yinchuan, Northwest China: a time series study.

BACKGROUND: Various nonpharmaceutical interventions (NPIs) against COVID-19 continue to have an impact on socioeconomic and population behaviour patterns. However, the effect of NPIs on notifiable infectious diseases remains inconclusive due to the variability of the disease spectrum, high-incidence endemic diseases and environmental factors across different geographical regions. Thus, it is of public health interest to explore the influence of NPIs on notifiable infectious diseases in Yinchuan, Northwest China. METHODS: Based on data on notifiable infectious diseases (NIDs), air pollutants, meteorological data, and the number of health institutional personnel in Yinchuan, we first fitted dynamic regression time series models to the incidence of NIDs from 2013 to 2019 and then estimated the incidence for 2020. Then, we compared the projected time series data with the observed incidence of NIDs in 2020. We calculated the relative reduction in NIDs at different emergency response levels in 2020 to identify the impacts of NIPs on NIDs in Yinchuan. RESULTS: A total of 15,711 cases of NIDs were reported in Yinchuan in 2020, which was 42.59% lower than the average annual number of cases from 2013 to 2019. Natural focal diseases and vector-borne infectious diseases showed an increasing trend, as the observed incidence in 2020 was 46.86% higher than the estimated cases. The observed number of cases changed in respiratory infectious diseases, intestinal infectious diseases and sexually transmitted or bloodborne diseases were 65.27%, 58.45% and 35.01% higher than the expected number, respectively. The NIDs with the highest reductions in each subgroup were hand, foot, and mouth disease (5854 cases), infectious diarrhoea (2157 cases) and scarlet fever (832 cases), respectively. In addition, it was also found that the expected relative reduction in NIDs in 2020 showed a decline across different emergency response levels, as the relative reduction dropped from 65.65% (95% CI: -65.86%, 80.84%) during the level 1 response to 52.72% (95% CI: 20.84%, 66.30%) during the level 3 response. CONCLUSIONS: The widespread implementation of NPIs in 2020 may have had significant inhibitory effects on the incidence of respiratory infectious diseases, intestinal infectious diseases and sexually transmitted or bloodborne diseases. The relative reduction in NIDs during different emergency response levels in 2020 showed a declining trend as the response level changed from level 1 to level 3. These results can serve as essential guidance for policy-makers and stakeholders to take specific actions to control infectious diseases and protect vulnerable populations in the future.

Exploring the interior of 3D endoluminal lesions in the air spaces by a novel electronic biopsy technique: A preliminary study of endoluminal colon lesions.

To explore the interior of a lesion in a 3D endoluminal view, this study investigates the application of an 'electronic biopsy' (EB) technique to computed tomographic colonography (CTC) for further differentiation and 2D image correlation of endoluminal lesions in the air spaces. A retrospective study of sixty-two various endoluminal lesions from thirty patients (13 males, 17 females; age range, 31 to 90 years) was approved by our institutional review board and evaluated. The endoluminal lesions were segmented using gray-level threshold and reconstructed into isosurfaces using a marching cube algorithm. EB allows users to interactively erode and apply grey-level mapping (GM) to the surface of the region of interest (ROI) in 3D CTC. Radiologists conducted the clinical evaluation, and the resulting data were analyzed. EB significantly improves 3D gray-level presentation for evaluating the surface and inside of endoluminal lesions over that of SR, GM or target GM (TGM) (P < 0.01) with preservation of the 3D spatial effect. Moreover, 3D to 2D image correlation were achieved in any layer of the lesion using EB as did GM/TGM on the surface. The specificity and diagnostic accuracy of EB are significantly greater than those of SR (P < 0.01). These performance can be better further with GM/TGM and reach the best with EB (specificity, 89.3-92.9%; accuracy, 95.2-96.8%). EB can be used in CTC to improve the differentiation of endoluminal lesions. EB increases 3D to 2D image correlations of the lesions on or beneath the lesion surface.

COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure.

BACKGROUND AND AIMS: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: Period of observation: March 1st, 2020 March 1st, 2021. INCLUSION CRITERIA: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up. RESULTS: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths. CONCLUSIONS: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.

Care of patients on home parenteral nutrition during the first year of the COVID-19 pandemic: Management of central line-associated bloodstream infections.

BACKGROUND AND AIM: The aim of this study was to analyze central line-associated bloodstream infections (CLABSI) in home parenteral nutrition (HPN) patients assisted by an interdisciplinary team during the first year of the COVID-19 pandemic in Argentina. METHODS: Longitudinal, retrospective and analytical study of patients on HPN for ≥90 days during 2020. Data collection included age (adults >18 years, pediatric ≤18 years), gender, diagnosis, type of catheter, number of lumens, venous access, days on HPN, infusion modality and number of CLABSI-associated events. In COVID-19 cases, number of patients, disease progression, mortality rate and microorganisms involved were analyzed. RESULTS: A total of 380 patients were included, 120 (31.6%) pediatric and 260 (68.4%) adult patients. Median age was 44.50 years (10; 62.25). Twelve patients (3.15% of the total) had COVID-19; of these, two pediatric and seven adult patients had no complications, and three adults died of COVID-19 pneumonia. The diagnoses observed were benign chronic intestinal failure (CIF, n = 311), grouped into short bowel (n = 214, 56.3%), intestinal dysmotility (n = 56, 14.7%), intestinal fistula (n = 20, 5.3%), and extensive small bowel mucosal disease (n = 21, 5.5%); malignant tumors (n = 52, 13.7%); other (n = 17, 4.4%). Total catheter days were 103,702. Median days of PN duration per patient were 366 (176.2, 366). The types of catheters used were tunneled (317 patients, 83.4%); peripherally inserted central (PICC) line (55 patients, 14.5%) and ports (8 patients; 2.1%). A total of 111 CLABSI was registered, with a prevalence of 1.09/1000 catheter days (adult, 0.86/1000 days; pediatric, 1.51/1000 days). The microorganisms identified in infectious events were Gram + bacteria (38, 34.5%); Gram-bacteria (36, 32%); mycotic (10, 9%); polymicrobial (4, 3.6%); negative culture and signs/symptoms of CLABSI (23, 20.3%). The odds ratio between pediatric and adult patients was 2.29 (1.35, 3.90). CONCLUSION: The rate of CLABSI during the COVID-19 pandemic was within the ranges reported by international scientific societies. The risk of CLABSI was higher in pediatric patients, and mortality rate in COVID-19 infected patients was higher than in the general population.

The role of IL-36 subfamily in intestinal disease.

Interleukin (IL)-36 is a subfamily, of the IL-1 super-family and includes IL-36α, IL-36ß, IL-36γ, IL-38 and IL-36Ra. IL-36 cytokines are involved in the pathology of multiple tissues, including skin, lung, oral cavity, intestine, kidneys and joints. Recent studies suggest that IL-36 signaling regulates autoimmune disease in addition to antibacterial and antiviral responses. Most research has focused on IL-36 in skin diseases such as psoriasis, however, studies on intestinal diseases are also underway. This review outlines what is known about the bioactivity of the IL-36 subfamily and its role in the pathogenesis of intestinal diseases such as inflammatory bowel disease, colorectal cancer, gut dysbacteriosis and infection, and proposes that IL-36 may be a target for novel therapeutic strategies to prevent or treat intestinal diseases.

Porcine intraepithelial lymphocytes undergo migration and produce an antiviral response following intestinal virus infection.

The location of intraepithelial lymphocytes (IELs) between epithelial cells provide a first line of immune defense against enteric infection. It is assumed that IELs migrate only along the basement membrane or into the lateral intercellular space (LIS) between epithelial cells. Here, we identify a unique transepithelial migration of porcine IELs as they move to the free surface of the intestinal epithelia. The major causative agent of neonatal diarrhea in piglets, porcine epidemic diarrhea virus (PEDV), increases the number of IELs entering the LIS and free surface of the intestinal epithelia, driven by chemokine CCL2 secreted from virus-infected intestinal epithelial cells. Remarkably, only virus pre-activated IELs inhibits PEDV infection and their antiviral activity depends on the further activation by virus-infected cells. Although high levels of perforin is detected in the co-culture system, the antiviral function of activated IELs is mainly mediated by IFN-γ secretion inducing robust antiviral response in virus-infected cells. Our results uncover a unique migratory behavior of porcine IELs as well as their protective role in the defense against intestinal infection.

SARS-CoV-2 Omicron BA.1 variant infection of human colon epithelial cells (preprint)

Omicron B.1.1.529 became the predominant SARS-CoV-2 variant in early 2022, causing a new wave of public anxiety. Compared to the ancestral strain, Omicron has 50 mutations, with over 30 mutations in the spike protein. These differences likely underlie the changes in Omicron biology noted in other studies, including an attenuation in the lung parenchyma, compared to the ancestral SARS-CoV-2 strain and other variants, as well as a preference for endosomal entry, in place of the TMPRSS2-mediated membrane fusion pathway. This raises questions on Omicron tropism and infectivity in various target organ systems, including the gastrointestinal (GI) tract. Up to 70% of COVID-19 patients report GI symptoms, including nausea, vomiting, and diarrhea. Here, we show that in the context of donor intrinsic genetic heterogeneity, the SARS-CoV-2 Omicron variant infects human colonoids similarly, if not less effectively, than the ancestral WT (WA1) strain or the Delta variant. Additionally, we note a higher ratio of viral RNA to infectious virus titer, which may suggest that Omicron is potentially less infectious in the intestine. This study lays the foundation for further work defining mechanisms mediating intestinal infection and pathogenesis by Omicron.

Intended healthcare utilisation in cases of severe COVID-19 and inflammatory gastrointestinal disease: results of a population survey with vignettes.

OBJECTIVES: To examine variations in intended healthcare utilisation in severe cases of COVID-19 and inflammatory gastrointestinal disease (IGD). DESIGN: Representative cross-sectional telephone survey. SETTING AND PARTICIPANTS: 1207 randomly drawn adults of the city of Hamburg, Germany, between November 2020 and January 2021. OUTCOME MEASURES: Different vignettes with severe symptoms were presented varying in sex, age (child, middle-aged person, older person), daytime (Tuesday morning or Tuesday evening) and disease (COVID-19 or IGD), while the degree of urgency was equivalent for all cases. The respondents were asked for the intended healthcare utilisation resulting in three different alternatives: general practitioner (GP)/paediatrician, medical on-call service ('116117') and emergency care (accident and emergency department, emergency practice, rescue service). In multivariate analyses, associations of characteristics of the vignettes and participants (sex, age, education, migration background) with intended healthcare utilisation were tested. In a further step, analyses were conducted separately for IGD and COVID-19. RESULTS: Regarding the vignettes' characteristics, intended utilisation of GP/paediatrician is associated with female sex, higher age, daytime (morning) and COVID-19 symptoms, the medical on-call service with male sex, daytime (evening) and COVID-19 symptoms and the emergency medicine with younger age, daytime (evening) and IGD. Women chose more often the GP/paediatrician, men preferred emergency medicine. Only in case of IGD, higher educated persons more often chose the medical on-call service while people with a migration background decided less often for medical on-call service and emergency medicine. CONCLUSIONS: Despite comparable urgency, the findings suggest variations of intended healthcare utilisation depending on various characteristics of the vignettes and respondents. Depending on the type of disease inequalities vary. Overall, information about healthcare alternatives in severe cases has to be improved and clear pathways to facilitate healthcare utilisation has to be further developed.

Bowel Ischemia in COVID-19 Infection: One-Year Surgical Experience.

BACKGROUND: COVID-19 is a deadly multisystemic disease, and bowel ischemia, the most consequential gastrointestinal manifestation, remains poorly described. Our goal is to describe our institution's surgical experience with management of bowel ischemia due to COVID-19 infection over a one-year period. METHODS: All patients admitted to our institution between March 2020 and March 2021 for treatment of COVID-19 infection and who underwent exploratory laparotomy with intra-operative confirmation of bowel ischemia were included. Data from the medical records were analyzed. RESULTS: Twenty patients were included. Eighty percent had a new or increasing vasopressor requirement, 70% had abdominal distension, and 50% had increased gastric residuals. Intra-operatively, ischemia affected the large bowel in 80% of cases, the small bowel in 60%, and both in 40%. Sixty five percent had an initial damage control laparotomy. Most of the resected bowel specimens had a characteristic appearance at the time of surgery, with a yellow discoloration, small areas of antimesenteric necrosis, and very sharp borders. Histologically, the bowel specimens frequently have fibrin thrombi in the small submucosal and mucosal blood vessels in areas of mucosal necrosis. Overall mortality in this cohort was 33%. Forty percent of patients had a thromboembolic complication overall with 88% of these developing a thromboembolic phenomenon despite being on prophylactic pre-operative anticoagulation. CONCLUSION: Bowel ischemia is a potentially lethal complication of COVID-19 infection with typical gross and histologic characteristics. Suspicious clinical features that should trigger surgical evaluation include a new or increasing vasopressor requirement, abdominal distension, and intolerance of gastric feeds.

High association of COVID-19 severity with poor gut health score in Lebanese patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected millions of lives globally. However, the disease has presented more extreme challenges for developing countries that are experiencing economic crises. Studies on COVID-19 symptoms and gut health are scarce and have not fully analyzed possible associations between gut health and disease pathophysiology. Therefore, this study aimed to demonstrate a potential association between gut health and COVID-19 severity in the Lebanese community, which has been experiencing a severe economic crisis. METHODS: This cross-sectional study investigated SARS-CoV-2 PCR-positive Lebanese patients. Participants were interviewed and gut health, COVID-19 symptoms, and different metrics were analyzed using simple and multiple logistic regression models. RESULTS: Analysis of the data showed that 25% of participants were asymptomatic, while an equal proportion experienced severe symptoms, including dyspnea (22.7%), oxygen need (7.5%), and hospitalization (3.1%). The mean age of the participants was 38.3 ±0.8 years, and the majority were males (63.9%), married (68.2%), and currently employed (66.7%). A negative correlation was found between gut health score and COVID-19 symptoms (Kendall's tau-b = -0.153, P = 0.004); indicating that low gut health was associated with more severe COVID-19 cases. Additionally, participants who reported unhealthy food intake were more likely to experience severe symptoms (Kendall's tau-b = 0.118, P = 0.049). When all items were taken into consideration, multiple ordinal logistic regression models showed a significant association between COVID-19 symptoms and each of the following variables: working status, flu-like illness episodes, and gut health score. COVID-19 severe symptoms were more common among patients having poor gut health scores (OR:1.31, 95%CI:1.07-1.61; P = 0.008), experiencing more than one episode of flu-like illness per year (OR:2.85, 95%CI:1.58-5.15; P = 0.001), and owning a job (OR:2.00, 95%CI:1.1-3.65; P = 0.023). CONCLUSIONS: To our knowledge, this is the first study that showed the impact of gut health and exposure to respiratory viruses on COVID-19 severity in Lebanon. These findings can facilitate combating the pandemic in Lebanon.

Ghost Ileostomy in Anterior Resection for Bowel Endometriosis: Technical Description.

OBJECTIVE: To demonstrate our application of the ghost ileostomy in the setting of laparoscopic segmental bowel resection for symptomatic bowel endometriosis nodule. DESIGN: Technical step-by-step surgical video description (educative video) SETTING: University Tertiary Hospital. Institutional Review Board ruled that approval was not required for this study. Endometriosis affects the bowel in 3% to 37% of all cases, and in 90% of these cases, the rectum or sigmoid colon is also involved. Infiltration up to the rectal mucosa and invasion of >50% of the circumference have been suggested as an indication for bowel resection [1]. Apart from general risks (bleeding, infection, direct organ injuries) and bowel and bladder dysfunctions, anastomotic leakage is one of the most severe complications. In women with bowel and vaginal mucosa endometriosis involvement, there is a risk of rectovaginal fistula after concomitant rectum and vagina resections. Hence, for lower colorectal anastomosis, the use of temporary protective ileostomy is usually recommended to prevent these complications but carries on stoma-related risks, such as hernia, retraction, dehydration, prolapse, and necrosis. Ghost ileostomy is a specific technique, first described in 2010, that gives an easy and safe option to prevent anastomotic leakage with maximum preservation of the patient's quality of life [2]. In case of anastomotic leakage, the ghost (or virtual) ileostomy is converted, under local anesthesia, into a loop (real) ileostomy by extracting the isolated loop through an adequate abdominal wall opening. In principle, avoiding readmission for performing the closure of the ileostomy, with all the costs related, means a considerable saving for the hospital management. Also, applying a protective rectal tube in intestinal anastomosis may have a beneficial effect [3]. These options are performed by general surgeons in oncological scenarios, but their use in endometriosis has never been described. INTERVENTIONS: In a 32-year-old woman with intense dysmenorrhea, deep dyspareunia, dyschesia, and cyclic rectal bleeding, a complete laparoscopic approach was performed using blunt and sharp dissection with cold scissors, bipolar dissector and a 5-mm LigaSure Advance (Covidien, Valley lab, Norwalk, Connecticut). An extensive adhesiolysis restoring the pelvic anatomy and endometriosis excision was done. Afterward, the segmental bowel resection was performed using linear and circular endo-anal stapler technique with immediate end-to-end bowel anastomosis and transit reconstitution. Once anastomosis was done, the terminal ileal loop was identified, and a window was made in the adjacent mesentery. Then, an elastic tape (vessel loop) was passed around the ileal loop, brought out of the abdomen through the right iliac fossa 5-mm port site incision and, fixed to the abdominal wall using nonabsorbable stitches. Finally, a trans-anal tube was placed for 5 days. The patient was discharged on the fifth day postoperatively without any complications. The tape was removed 10 days after surgery, and the loop dropped back. Two months after the intervention, the patient remains asymptomatic. CONCLUSION: Ghost ileostomy is a simple, safe, and feasible technique available in the setting of lower colorectal anastomosis following bowel endometriosis resection.

Human small intestinal infection by SARS-CoV-2 is characterized by a mucosal infiltration with activated CD8+ T cells.

The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells has recently been demonstrated, it remains unclear, whether gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or whether they are a consequence of a systemic immune activation and subsequent modulation of the mucosal immune system. To better understand the cause of intestinal symptoms we analyzed biopsies of the small intestine from SARS-CoV-2 infected individuals. Applying qRT-PCR and immunohistochemistry, we detected SARS-CoV-2 RNA and nucleocapsid protein in duodenal mucosa. In addition, applying imaging mass cytometry and immunohistochemistry, we identified histomorphological changes of the epithelium, which were characterized by an accumulation of activated intraepithelial CD8+ T cells as well as epithelial apoptosis and subsequent regenerative proliferation in the small intestine of COVID-19 patients. In summary, our findings indicate that intraepithelial CD8+ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.

Intestinal Abnormalities in Patients With SARS-CoV-2 Infection: Histopathologic Changes Reflect Mechanisms of Disease.

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.

Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip (preprint)

Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PMBCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

Cefaclor Monohydrate-Loaded Colon-Targeted Nanoparticles for Use in COVID-19 Dependent Coinfections and Intestinal Symptoms: Formulation, Characterization, Release Kinetics, and Antimicrobial Activity.

Corona virus disease-2019 (COVID-19) emerged in Wuhan, China in December 2019 and was declared as a pandemic by the World Health Organization in March 2020. Although there is no complete treatment protocol for COVID-19, studies on this topic are ongoing, and it is known that broad-spectrum antibiotics such as cephalosporins are used for coinfections and symptoms in COVID-19 patients. Studies have shown that Staphylococcus aureus and Escherichia coli bacteria can cause symptoms such as diarrhea and coinfections accompanying COVID-19. Therefore, in this study, colon-targeted cefaclor monohydrate (CEF)-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit S100 nanoparticles (NPs) were prepared using a nanoprecipitation technique. The particle sizes of the CEF-loaded NPs were between 171.4 and 198.8 nm. The encapsulation efficiency was in the range of 58.4%-81.2%. With dissolution studies, it has been concluded that formulations prepared with Eudragit S100 (E-coded) and Eudragit S100+PLGA (EP-coded) are pH-sensitive formulations and they are targetable to the colon, whereas the formulation prepared only with PLGA (P-coded) can release a higher CEF rate in the colon owing to the slow release properties of PLGA. The release kinetics were fitted to the Korsmeyer-Peppas and Weibull models. The antibacterial activity of E-, EP-, and P-coded formulations was 16-fold, 16-fold, and 2-fold higher than CEF, respectively, for S. aureus and E. coli according to the microdilution results. As a result of the time killing experiment, all formulations prepared were found to be more effective than the antibiotic itself for long periods. Consequently, all formulations prepared in this study hope to guide researchers/clinicians in treating both gram-positive and gram-negative bacteria-induced infections, as well as COVID-19 associated coinfections and symptoms.

The EPAGE guidelines are not an effective strategy for managing colonoscopies during the COVID-19 pandemic. / EPAGE no es una estrategia eficaz para la gestión de colonoscopias durante la pandemia por COVID-19.

INTRODUCTION: The pandemic caused by the SARS-CoV-2 virus has had a serious impact on the functioning of gastrointestinal endoscopy Units. The Asociación Española de Gastroenterología (AEG) and the Sociedad Española de Endoscopia Digestiva (SEED) have proposed the EPAGE guidelines for managing postponed colonoscopies. OBJECTIVE: To evaluate the EPAGE guidelines as a management tool compared to the immunologic faecal occult blood test (iFOBT) and compared to risk score (RS) that combines age, sex and the iFOBT for the detection of colorectal cancer (CRC) and significant bowel disease (SBD). METHODS: A prospective, single-centre study enrolling 743 symptomatic patients referred for a diagnostic colonoscopy. Each order was classified according to the EPAGE guidelines as appropriate, indeterminate or inappropriate. Patients underwent an iFOBT and had their RS calculated. RESULTS: The iFOBT (p<0.001), but not the EPAGE guidelines (p = 0.742), was an independent predictive factor of risk of CRC. The ROC AUCs for the EPAGE guidelines, the iFOBT and the RS were 0.61 (95% CI 0.49-0.75), 0.95 (0.93-0.97) and 0.90 (0.87-0.93) for CRC, and 0.55 (0.49-0.61), 0.75 (0.69-0.813) and 0.78 (0.73-0.83) for SBD, respectively. The numbers of colonoscopies needed to detect a case of CRC and a case of SBD were 38 and seven for the EPAGE guidelines, seven and two for the iFOBT, and 19 and four for a RS ≥5 points, respectively. CONCLUSION: The EPAGE guidelines, unlike the iFOBT, is not suitable for screening candidate patients for a diagnostic colonoscopy to detect CRC. The iFOBT, in combination with age and sex, is the most suitable strategy for managing demand for endoscopy in a restricted-access situation.

Bowel necrosis in patient with severe case of COVID-19: a case report.

BACKGROUND: In patients who are critically ill with COVID-19, multiple extrapulmonary manifestations of the disease have been observed, including gastrointestinal manifestations. CASE PRESENTATION: We present a case of a 65 year old man with severe COVID-19 pneumonia that developed hypercoagulation and peritonitis. Emergent laparotomy was performed and we found bowel necrosis in two sites. CONCLUSIONS: Although rare, the presentation of COVID-19 with bowel necrosis requires emergency treatments, and it has high mortality rate.